Reconstituting device for injectable medication

ABSTRACT

A device for reconstituting liquid for medical use by bringing together a first liquid medium contained in a first vessel in the form of a cartridge ( 3 ) and a second medium, such as a drug in solid form, contained in a second vessel in the form of a vial ( 7 ), the device ( 19 ) comprising means ( 41 ) for supporting the first and second vessels, and a movable operating member ( 50 ) for applying a force to cause the first liquid medium to be delivered at a controlled rate from the first vessel into the second vessel. The first and second vessels may be provided in a pack ( 70 ) having liquid transfer means in the form of a needle ( 10 ).

The present invention relates to a device, a pack and a kit forreconstituting a liquid for medical use, such as a parenteral orpharmaceutical liquid.

It is common practice for people requiring frequent parenteraladministration of drugs to be provided with home-use kits containingautoinjectors which may be used for the purposes of self-administration.Liquid formulations of drugs are however seldom stable over prolongedperiods of time and it is common for the drug itself to be provided in asolid form eg. a lyophilised (i.e. freeze dried), dehydrated orcrystalline form. Typically, a user might be provided with a two weeks'supply of a lyophilised drug in sealed vials together with a supply ofcartridges containing diluent. However, one problem associated withconventional autoinjector devices is the lengthy procedure (in excess of40 steps) needed to reconstitute the solid drug into a liquidformulation prior to administration.

A known drug reconstitution device is illustrated in FIG. 1 of theaccompanying drawings. In normal use, a plunger pin 1 is screwed into aplunger 2 in a cartridge 3 which contains a diluent for the drug. Thecartridge 3 is placed into a barrel 4 of a dismantled autoinjector and acollar 5 is screwed onto a thread 11 thereby holding the cartridgeinside the barrel 4, with the plunger pin projecting outwardly of thebarrel. A vial 7 containing a drug in solid form has a flip-off plasticseal 7 b on a bung 7 a. The seal 7 b is removed and the exposed portionof the bung is sterilised with an alcohol swab. The drug vial 7 is slidinto the end of an adapter 8. A needle 10 is screwed onto a thread 6 aof the barrel 4 and an outer needle cover 12 and an inner needle cover13 are removed. The adapter 8 is then screwed onto a thread 6 of thebarrel 4, at which time the needle 10 penetrates the bung 7 a of thedrug vial 7.

To effect reconstitution of the drug formulation, the complete assemblyis held vertically with the needle pointing upwards and the plunger pin1 is gently depressed thereby injecting the contents of the cartridge 3into the vial 7. The whole assembly is inverted and typically left tostand for 5 minutes to ensure complete dissolution of the drug. Afterensuring that the plunger pin 1 is fully depressed the complete assemblyis held vertically with the needle pointing upwards and the plunger pin1 is gently pulled out thus drawing the constituted drug formulationinto the cartridge. The vial adapter 8 is then unscrewed from thread 6and discarded along with the empty vial 7. With the needle pointingvertically upwards, the plunger pin 1 is gently depressed until a fewdroplets of liquid appear at the end of the needle to ensure that anyair trapped within the cartridge is removed. The inner needle cover 13and the outer needle cover 12 are replaced onto the needle prior to theneedle 10 being unscrewed from thread 6 a and discarded. The plunger pin1 is unscrewed from the plunger 2 and the collar 5 from thread 11 andboth may be discarded. The reconstitution process is now complete andthe charged cartridge may be loaded into an autoinjector which may bere-assembled and primed ready for use.

Added to the problem of the lengthy reconstitution procedure, it hasalso been observed with devices of this type that foaming may occur whenthe cartridge contents are introduced to the vial. This undesirableeffect is limited to a certain degree provided that the user follows therecommended procedure and holds the assembly with the needle pointingupwards before gently depressing the plunger and injecting the liquidvertically upwards into the drug vial. However the lack of control whichthe user is generally able to exert over the transmission of the liquiddiluent onto the drug means there is still a considerable risk offoaming and associated unwanted effects, especially if the diluent isinjected into the vial too rapidly. It is difficult for the user to beable reliably to control the rate at which diluent passes into the vialto avoid foaming on each occasion that the device is used.

Thus viewed from one aspect the present invention provides a device forreconstituting a liquid for medical use by bringing together a firstliquid medium contained in a first vessel and a second medium containedin a second vessel, the device comprising means for supporting the firstand second vessels, and a movable operating member for applying a forceto cause the first liquid medium to be delivered at a controlled ratefrom the first vessel into the second vessel.

Since the device both supports the first and second vessels and providesa force for causing controlled delivery, this saves a user fromperforming these tasks and thus simplifies operation. In general, toorapid delivery can be avoided, substantially minimising effects such asfoaming with certain media.

The device according to the invention is most convenient forreconstituting solid drugs (e.g. lyophilised drugs in the form ofpowders or pastes and the like) into a liquid solution or suspensionusing appropriate solvents, diluents, carriers, etc. However, the deviceis equally useful for contacting a first liquid (or a first mixture ofliquids) with a second liquid or suspension or a mixture of liquidsand/or suspensions.

Particular examples of drugs which may be provided in a lyophilised forminclude growth hormone, fertility drugs, antibiotics (eg.cephalosporins) and renitidine.

Although the first and second vessels may take various forms, in onepreferred form of the invention the device is suitable for use with afirst vessel in the form of a cartridge with a movable plunger and asecond vessel in the form of a vial. The movable operating member of thedevice can then apply a force to move the plunger and thereby effectdelivery.

The media, once brought together, are preferably transferred from thesecond vessel to the first vessel. It is therefore particularlyconvenient for the device to be reversibly operable to deliver the mediaback to the first vessel, e.g. a cartridge, preferably with control ofthe rate of delivery, although control is not essential during returndelivery.

The movable operating member may be driven in various ways, includingbut not limited to, the use of compressed gas, one or more springs eg. aspring driven motor, or another form of motor eg. an electrically drivenmotor. In a preferred embodiment, a weight provides the force to effectdelivery. In another preferred embodiment, a spring is used.

The rate at which the movable operating member moves will be dependenton a number of factors. In general, the movable operating member will bedriven and its movement will be resisted by suitable damping means, forexample frictional damping means. In seeking to eliminate unwantedeffects such as foaming, it is possible to select e.g. a weight havingan appropriate mass or a spring having an appropriate spring constant toprovide the drive for the movable operating member and to selectcomponents with appropriate frictional interaction in order to give adegree of control over the speed at which liquid is delivered into thesecond vessel.

Alternative or additional forms of damping may be provided. Thus in afurther embodiment of the invention compressed gas may be provided toact against the delivery force whilst being allowed to escape from theregion in which it is confined (eg. by bleeding through a small vent).In one preferred embodiment, movement of the movable operating member iscontrolled at least partly by the flow of gas via a restricted flowpath. Alternatively or additionally, there may be hydraulic dampingmeans.

The flow path of the first liquid medium from the first to the secondvessel will also tend to introduce its own resistance to flow and willthus have an effect on the rate of delivery. This can be taken intoaccount when designing the device for use with a particular liquid flowpath (which may for example be provided by a needle or the like).Account may also be taken of the viscosity of the first liquid medium.

A switch or the like may be provided to initiate delivery. In onepreferred embodiment however delivery is initiated by inverting thedevice. Thus a gravity responsive switch may be provided to actuate e.g.a valve for compressed gas supply or a motor, but where the deliveryforce is provided by a weight a switch will not normally be needed. Inanother preferred embodiment in which the drive for the movableoperating member is provided by a spring, the spring may be primed andsimply released to initiate delivery, or it may be latched in the primedcondition.

There is preferably provided a common housing for the means forsupporting the first and second vessels and the movable operatingmember. The device is advantageously a self-contained and portable unit.

The movable operating member is preferably guided in its movement, forexample internally of a housing. In certain preferred embodiments, anarrangement of relatively movable coaxial tubular members is provided toguide the movement of the movable operating member. Thus the movableoperating member may be movable with a first tubular member which isguided by a second tubular member arranged either outside or inside thefirst tubular member. In the case where the second tubular member isoutside the first, the second tubular member may also conveniently formthe housing of the device.

In the case of a weight driven system, the second tubular member mayprovide the weight to effect delivery and it is then advantageous if itis coaxial with the movable operating member, as this can ensure thatload is applied along the axis of movement and not eccentrically.

In general, the movable operating member will be arranged to engage amovable portion of the first vessel to effect delivery, for example byengaging a wall of a bag, bladder, sachet or the like. Preferably themovable portion is urged in an axial direction. The movable portion mayfor example be a plunger of the first vessel. The movable operatingmember may be a plunger rod which screws into or otherwise engages sucha plunger. Frictional resistance to movement of the movable portion ofthe first vessel is a further factor which will tend to affect the rateof delivery of the first liquid medium into the second vessel.

An indicator is advantageously provided for indicating the status ofdelivery. The indicator may provide a visual indication of the positionof the movable operating member. Thus, for example, where the movableoperating member is located internally of a housing, the housing may beformed with a slot through which the movable operating member is visibleto indicate its position. The movable operating member may have aportion projecting through the slot. Alternatively, the indicator maytake the form of a timing mechanism independent of the movable operatingmember but which nevertheless provides an indication that delivery ofthe first liquid medium into the second vessel is complete. For example,in the case where delivery is initiated by inverting the device, anhourglass may be provided as the timing mechanism.

The device may be provided in combination with a pack removablyinsertable in the device. Such a combination forms a kit comprising thedevice and the pack. Such a kit is advantageous for a user because thepack is removable enabling re-use of the device.

Viewed from another aspect therefore the invention provides a kit forreconstituting a liquid for medical use by bringing together a firstliquid medium contained in a first vessel and a second medium containedin a second vessel, the kit comprising a pack for holding the first andsecond vessels, and a device in which the pack is removably insertable,the kit being operable to bring the first liquid medium and the secondmedium together.

In a preferred embodiment, the device has means for engaging the pack tocause the first and second vessels to be placed in liquid communication,preferably via liquid transfer means of the pack. This furthersimplifies operation by a user. The device may for example have a lidwhich as it is closed pushes against the pack and compresses it, therebycausing liquid communication, for example by a needle penetratingthrough a seal of the first vessel. Preferably, the device has means toensure that in use the liquid transfer means accesses the second vessel(which may e.g. contain a lyophilised powder) before it accesses thefirst vessel containing the liquid medium. Where the liquid transfermeans is a needle in this preferred embodiment, the fact that the needlepenetrates the second vessel before it penetrates the liquid mediumcontaining first vessel prevents the loss of liquid medium.

The pack may include at least the first vessel containing the firstliquid medium. The second vessel may be added to the pack by the user ormay be added during the manufacture and assembly of the pack, andpreferably therefore the pack includes the second vessel containing thesecond medium.

Preferably the first vessel is readily removable from the pack, so thatafter the reconstituted liquid has been returned to the first vessel therest of the pack can be safely disposed of. This reduces the number ofsteps for the user. In a preferred arrangement, the pack includes liquidtransfer means, such as a needle, for liquid transfer between thevessels and this is advantageously shielded by a housing of the pack.Since the liquid transfer means can be disposed of with the pack whilstin a shielded condition, there is improved safety over the known systemshown in FIG. 1 in which the needle itself had to be screwed onto andunscrewed from the barrel 4. There is thus increased safety in that thediscarded components cannot cause needle-stick injury, because theneedle is enclosed within the pack. The housing is preferablysleeve-shaped.

The shielding of the liquid transfer means is of independent patentablesignificance. Viewed from another aspect therefore the present inventionprovides a pack for reconstituting a liquid for medical use by bringingtogether a first liquid medium contained in a first vessel and a secondmedium contained in a second vessel, the pack comprising means forholding the first and second vessels, liquid transfer means for placingthe vessels in liquid communication, said liquid transfer meansincluding a penetrating member for penetrating a closure of the secondvessel, and means for shielding a user from the penetrating memberbefore, during and after liquid reconstitution.

A further problem with the known system shown in FIG. 1 is that theneedle covers 12 and 13 have to be removed prior to penetration of thebung 7 a of the drug vial 7 by the needle, so that the needle is exposedto a non-sterile environment. The potential for contamination is evenworse if the sharp end of the needle is actually handled by a user.

Viewed from a further aspect, therefore, the present invention providesa pack for reconstituting a liquid for medical use by bringing togethera first liquid medium contained in a first vessel and a second mediumcontained in a second vessel, the pack comprising means for holding thefirst and second vessels, liquid transfer means for placing the vesselsin liquid communication, said liquid transfer means including apenetrating member for penetrating a closure of the second vessel,wherein the penetrating member is arranged to be maintained in a sterileenvironment at all times prior to penetration of the second vesselclosure.

The second vessel closure may form one wall of a sterile chamber, whichwall is penetrated when it is desired to communicate the vessels, byrelative movement between the wall and the penetrating member. In apreferred arrangement, a protective member for the penetrating member isarranged such that when the penetrating member and the second vesselclosure are brought together the penetrating member penetrates both theprotective member and the second vessel closure.

The protective member may for example be a sheath on the penetratingmember. In use, the penetrating member will pierce the sheath as itpenetrates the second vessel closure.

Alternatively the protective member may be a bung which is preferablyarranged to be pushed onto the penetrating member by the second vessel.The bung may thus act in the manner of a piston or the like, movableinto a sterile chamber surrounding the penetrating member. There ispreferably provided means for venting gas from the sterile environmentaround the penetrating member when the bung is pushed, such as a bead ona wall of a cylinder in which the bung is slidably mounted.

In a convenient form of construction of the pack, the liquid transfermeans may be arranged in a tubular housing for receiving the firstvessel at one end and the second vessel at the opposite end.

The second vessel is preferably removably held by the pack. This enablesmore than one second vessel to be used with the first vessel, which isuseful for example to produce different concentrations of drug in adiluent.

It will be appreciated that the sterility of the penetrating member canbe maintained even if the second vessel is suppled separately of thepack for user assembly therewith. This may be advantageous in that thepack can be manufactured independently of the second vessel.

In one preferred form of the pack, the liquid transfer means includes asecond penetrating member for penetrating a closure of the first vessel.Thus the liquid transfer means may for example be a double ended needle.Such an arrangement may be useful if the first vessel is a cartridgeclosed at one end by a penetratable seal. The arrangement may be suchthat the sterility of the second penetration member is maintained at alltimes prior to penetration of the first vessel closure, as with thefirst mentioned penetrating member. This may be achieved by a protectivemember such as a sheath or a bung, even if the first vessel is suppliedseparately of the pack.

In another preferred form of the pack, the liquid transfer meansincludes a Luer fitting. This may be useful if the first vessel is apre-filled syringe. The Luer fitting may be kept sterile prior toinstallation of the first vessel by a paper or film seal or the like.

The pack may be provided with a removable cap which is preferably tamperevident. If the first vessel has a movable portion, such as a plunger,the cap preferably attaches to the pack housing adjacent to the movableportion. Thus removal of the cap enables the movable operating member ofthe device to engage the movable portion, preferably by a screw-fit.

It will be appreciated that the packs described above have advantagesover known constitution systems, such as that described in FIG. 1, whicharise independently of the liquid reconstitution device also described:Although the packs may be used with the device, they can also be used ontheir own, without the device. For example, a user may manually operatea plunger of a cartridge forming the first vessel to bring together thefirst and second media.

It is envisaged that the device, kit and pack according to the inventionin its various aspects will be used by doctors, dentists and the likebut particularly by home-users. The invention in a still further aspectthus provides use of a device as hereinbefore defined for reconstitutinga pharmaceutical liquid formulation, preferably a parenteral liquidformulation comprising a drug and a diluent or carrier.

Certain preferred embodiments of the invention will now be furtherdescribed by way of example and with reference to FIGS. 2 to 6 of theaccompanying drawings, in which:

FIG. 1 illustrates a known drug reconstruction device;

FIGS. 2a and 2 b show a fully assembled device according to oneembodiment of the invention;

FIGS. 3a to 3 d show a pack in various stages of assembly;

FIGS. 4a to 4 e show the assembled pack loaded into a device at variousstages of the constitution process;

FIG. 5 shows an alternative form of pack;

FIGS. 6a to 6 b show various stages of the liquid reconstitutionprocedure;

FIG. 7 shows an alternative form of a device for receiving a pack, in aneutral condition;

FIG. 8 shows the device of FIG. 7 in a condition primed for delivery;

FIG. 9 shows the device of FIG. 7 in a condition after liquid has beendelivered from a first vessel to a second vessel;

FIG. 10 shows the device of FIG. 7 in a condition primed for delivery ofthe liquid back to the first vessel;

FIGS. 11a to 11 i show various stages of the liquid reconstitutionprocedure using the device of FIG. 7;

FIG. 12 shows a further alternative form of pack;

FIG. 13 shows a sectional view of part of the pack of FIG. 12;

FIG. 14 shows a sectional view on the lines A—A of FIG. 13;

FIG. 15 shows a syringe formed using the cartridge shown in FIG. 12; and

FIG. 16 shows another form of pack.

A unitary pack 70 is shown in FIGS. 3b-3 d. This pack comprises a firstvessel, in the form of a diluent cartridge 3, and a sterile needle 10carried by a needle hub 10 a in a sleeve-shaped housing 17. Thecartridge 3 has a plunger 21 at one end and a seal 23 at the other end,adjacent the needle. The end of the needle hub 10 a nearest to thecartridge may conveniently be covered with any conventional seal 15,such as a paper seal, for example a Tyvek (registered trade mark) seal,to retain its sterility and its other end 16 may be protected by forexample a rubber sheath (not shown) to retain sterility. A tamperevident cap 18 closes the end of the housing 17 adjacent the cartridge3. At the other end of the housing there is disposed a second vessel, inthe form of a vial 7 sealed by a bung 24, containing a drug in solidform.

An alternative pack is illustrated in FIG. 5. As shown in FIG. 5, thehousing 17 may conveniently be provided with a retention lip 31 whichprevents a drug vial 7 being removed from the pack once it has beeninserted. A seal 30 closes the end of the housing where the vial 7 is tobe inserted. A tamper evident label 32 extends across the join betweenthe housing and the cap 18.

FIGS. 2a, 2 b and 4 a-4 e show a device 19 into which the pack 70 isremovably insertable. The device 19 has a housing 62 having a screwfitted lid 40 provided with a recess 41 in which the portion of the packholding the vial 7 engages. Internally of the housing 62 there isprovided control means comprising an operating member in the form of aplunger rod 50 and a tubular weight 20 arranged coaxially therewith. Theplunger rod 50 has a threaded end for screwing into the plunger 21. Anexternally projecting member 60 projects from the tubular weight 20through a slot 61 in the housing 62 of the device 19.

In use, the operator removes a flip-off cover (not shown) from the topof a bung 24 of the drug vial 7 and the seal 30 (see FIG. 5) from theend of pack housing is 17 and, after ensuring the sterility of the bung24 in the vial, clips the vial into the end of the pack 70. The tamperevident cap 18 is removed from the pack and the pack is inserted intothe reconstitution device 19 shown in FIGS. 4a-4 e. It is screwed intoposition, so that the plunger rod 50 screws into the plunger 21.

In the preferred arrangement illustrated in FIGS. 4a-4 e, the device isarranged to compress the pack, from its initial length to the length “L”shown in FIG. 3d. This forces the end 16 of the needle through itsrubber sheath and then through the bung 24 on the top of vial 7. Theseal 23 of the cartridge is forced through the seal 15 of the needle huband is then penetrated by the needle 10. The compression is achieved bythe lid 40 as it is screwed into place.

The situation after the needle 10 has penetrated through the bung 24 andthe seal 23 is shown in FIG. 4a (and FIG. 2a). The further steps in theprocess will be described with reference to FIGS. 4b-4 e.

The device 19 is inverted to adopt the position shown in FIG. 4b andthis causes the tubular weight 20 to move under the effect of gravity,depressing plunger 21 in the cartridge and thereby forcing diluent 22into the vial 7. The device adopts the position shown in FIG. 4c (and 2b). The weight 20 is arranged to cause the smooth, gentle movement ofplunger 21. The weight therefore provides the drive of the controlmeans. The drive is thus effected in a controlled manner, substantiallyautomatically and independently of the user, who simply has to invertthe device to initiate the process.

The device is left to stand for several minutes in the position shown inFIG. 4c to ensure the complete dissolution of the drug and then invertedonce more to the position shown in FIG. 4d. This results in weight 20again moving under the effect of gravity, withdrawing plunger 21 andthereby drawing the constituted drug back into the cartridge 22, asshown in FIG. 4e. Disassembly of device 19 allows the pack 70 to beremoved therefrom and the cartridge 22 from pack 70, leaving needle 10and vial 7 in pack 70 for safe disposal. Cartridge 22 is then placed inthe autoinjector which is re-assembled and primed for use.

The device is also usefully provided with an externally viewableindicator for indicating the position of the weight so that the user ismade aware of when to re-invert the device. This is provided by themember 60 projecting through the slot 61. Alternatively, a timing devicesuch as an hour-glass may be incorporated which is independent of themovement of the control means.

The embodiment described above has the advantage of allowingconstitution in a significantly reduced number of steps to that possiblewith prior art devices. Thus the process of reconstitution in thisembodiment is as follows:

1. Open the pack;

2. Remove the flip-off from the drug vial;

3. Insert the drug vial into the pack after ensuring the sterility ofthe seal on the vial;

4. Insert the pack into the device;

5. Invert the device and leave to stand;

6. Invert the device;

7. Remove the pack; and

8. Remove the cartridge from the pack and use as directed by thephysician.

It will be noted that the device is reusable and portable.

A preferred arrangement for achieving sequential liquid communicationbetween first and second vessels is illustrated in various stages of theprocedure in FIGS. 6a-6 b. Thus FIG. 6a shows a pack 70 in the initialposition prior to compression. A needle 10 is supported by needle hub 10a which is itself supported at the inner end of a diluent cartridge 3,the inner end of which is closed by a seal 23. A plunger 21 is providedat the outer end of the cartridge 3 and is threaded to receive a plungerrod 50 which may be an integral part of a device 19 as describedhereinbefore. A sleeve shaped housing 17 is provided with a cross-member17 a having an opening 17 b large enough to receive the needle 10. Avial 7 sealed by a bung 24 is disposed on the side of the cross-member17 a remote from the cartridge 3. Needle hub 10 a is in two portions,namely a protruding portion 10 b which is capable of collapsing within abase portion 10 c when sufficient force is applied to break a frangibleportion 10 d by which the two portions are adjoined.

FIG. 6b shows the arrangement in an intermediate position in which thelid 40 of the device 19 has been partially screwed into place, causingthe pack 70 to compress. During the compression movement, the housing 17and the vial 7 move axially towards the cartridge 3 until the protrudingportion 10 b of the needle hub is engaged against the cross-member 17 a,as seen in FIG. 6b. The needle 10 passes through opening 17 b topenetrate bung 24 of vial 7.

Further screwing of the lid 40 of the device 19 into a fully closedposition completes the compression of the pack 70. The cross-member 17 apushes the protruding portion 10 b towards the cartridge 3, therebybreaking the frangible portion 10 d and forcing the protruding portion10 b to collapse into the base portion 10 c. The final position in whichliquid communication is achieved is shown in FIG. 6b wherein theprotruding portion 10 b has collapsed wholly within the base portion 10c and the needle 10 has penetrated the seal 23 of the liquid carryingcartridge 3.

Thus the above-described arrangement ensures that the needle 10penetrates the bung 24 of the vial before it penetrates the seal 23 ofthe cartridge, thereby avoiding any accidental loss of liquid from thecartridge.

FIG. 7 shows an alternative form of a device 19 for receiving a pack 70,in a neutral condition and before a pack has been added. The principaldifference between this device and the one shown in FIGS. 2a, 2 b and 4a-4 e is that the FIG. 7 device is driven by a spring 80, rather than bya weight. This enables the overall device to be lighter and henceparticularly convenient to use.

The device 19 has a housing 62 having a lid 40 provided with an externalthread 41 a in which the portion of a pack holding a vial 7 is to engage(e.g. thread 131 shown in FIG. 12). Internally of the housing 62 thereis provided a plunger rod assembly including a plunger rod 50 secured bya screw fitting 81 to a plunger hub 82. An air flow path 83 passesthrough the plunger hub so as to vent a plunger chamber 84 toatmosphere. The air flow path 83 is provided with a pair of paperfilters 85,86 which provide a resistance to air flow across the filtersand also maintain the cleanliness of plunger chamber 84.

The top end of the plunger rod 50 (as seen in FIG. 7) passes through anopening 87 formed at the lower end of an inner guide tube 88, which isfixed to the external housing 62. The opening 87 is provided with aplunger rod seal 89. The top of the plunger rod is formed with a malethread 110. An outer guide tube 90 extends upwardly from and is fixed tothe plunger hub 82 so as to be movable therewith. The outer guide tube90 is arranged to be guided on inner guide tube 88. A shoulder 93 isprovided at the top of outer guide tube 90 and extending upwardly of theshoulder 93 the plunger rod assembly has an indicator flag 96.

A collar 91 is arranged outwardly of outer guide tube 90 so as to beaxially movable relative thereto. The spring 80 engages a lower flangeof the collar at its lower end and at its upper end it engages both theshoulder 93 of the plunger rod assembly and a shoulder 94 of anactuating assembly 95.

The collar 91 is slidably supported on the actuating assembly 95 so asto be movable between a lower limit position as seen in FIGS. 7, 8 and 9and an upper limit position as seen in FIG. 10. The actuating assemblyfurther comprises an inner portion 97 on which the shoulder 94 is formedand which is movable axially inside the housing 62, and an outer sleeve98 axially movable with the inner portion but situated outwardly of thehousing 62.

A lower latch 100 and an upper latch 101 are disposed on the outersleeve 98 of the actuating assembly. A leaf spring 102 is arranged tourge an upper end of the lower latch 100 and a lower end of the upperlatch 101 radially inwardly. The lower latch 100 is arranged to rockabout a horizontal axis on a pivot 103, whilst a corresponding pivot 104is provided for the upper latch 101. Each latch is provided with arespective operating knob 105,106. Detents 120,121 are provided on thehousing for engagement by the respective latches 100,101.

FIGS. 11a-11 i show various stages of the liquid reconstitutionprocedure using the device of FIG. 7. The procedure will now bedescribed with reference to FIGS. 7-10 and 11 a-11 i. The device in itsinitial condition, without a pack, is shown in FIG. 11a. The lid 40 isunscrewed, as shown in FIG. 11b, and a pack is screwed into place, witha female thread 130 in a plunger 21 (see FIG. 12) receiving the malethread 110 at the top of the plunger rod 50. The lid 40 is screwed ontothe exposed end of the pack, to adopt the position shown in FIG. 11c.The device is inverted to adopt the position shown in FIG. 11d andoperating knob 105 of latch 100 is depressed to cause disengagement ofthe latch from detent 120. This releases the actuating assembly so thatit can be slid downwardly to the position shown in FIG. 11e. The deviceis then in the condition primed for delivery shown in FIG. 8, with latch101 engaged on detent 121. It will be seen from FIG. 8 that in thisprimed condition spring 80 is compressed.

Since collar 91 is in its lower limit position it cannot move and thusas spring 80 expands it pushes the plunger rod assembly downwardly(upwardly as viewed in FIG. 8) so as to push liquid from the cartridge22 into the vial 7. The rate at which the plunger rod assembly moves isdetermined by the rate of air venting from plunger chamber 84 via theair flow path 83 provided with air filters 85,86. The smaller the poresize of these filters the slower the rate of movement of the plunger rodassembly and a typical target time for the total movement is about 2-3minutes. As the plunger rod assembly moves downwardly the indicator flag96 moves downwardly through a slot in the housing 62 so as to be visiblethrough a transparent portion of the lid 40. Use of appropriate graphicson the indicator flag shows when liquid transfer from the cartridge tothe vial is complete. This condition is shown in FIGS. 11f and 9. Itwill be seen that latch 101 engages detent 121.

In the next step the device is inverted to adopt the position shown inFIG. 11g. The user depresses operating knob 106 to release latch 101from detent 121 and slides the actuating assembly downwardly until latch102 engages detent 120, as shown in FIGS. 11h and 10. Again thiscompresses spring 80 which then expands and pushes the plunger rodassembly downwardly, so that the reconstituted liquid is sucked from thevial back into the cartridge. When the indicator flag 96 disappears,liquid transfer back to the cartridge is complete, as shown in FIG. 11i.The time taken for return liquid transfer is typically 1-3 minutes. Thelid 40 is unscrewed from the device and the pack is unscrewed from thedevice. The cartridge, now containing the dissolved drug, is removedfrom the pack and the rest of the pack is discarded. The lid 40 may bescrewed back onto the device ready for future use.

A form of pack suitable for use in the device of FIG. 7 is shown in FIG.12. The pack 70 holds a first vessel, in the form of a diluent cartridge3, and a second vessel in the form of a drug vial 7. The cartridge 3 hasa plunger 21 formed with a female screw thread 130 (for engagement withmale screw thread 110 of plunger rod 50 shown in FIG. 7). At the otherend the cartridge 3 has a seal 23. The pack 70 has a sleeve shapedhousing 17 formed at its end for receiving the drug vial 7 with a thread131 suitable for engagement with thread 41 a shown in FIG. 7. Prior toinstallation of the vial 7, the end of the housing is sealed by a filmor paper seal 30. At its other end the pack has a cap 18 which closesthe end of the housing 17 adjacent the cartridge 3. When the pack is tobe inserted in a device 19 the cap 18 is removed whereby the cartridge 3protrudes from the housing 17.

A needle assembly 140 is located at a fixed position within housing 17.Referring to FIGS. 13 and 14, the needle assembly 140 comprises a needlehub which is generally “H” shaped in longitudinal cross-section,supporting a double-ended needled 10. A web 141 supports the needle 10and is formed with apertures 142 which communicate upper and lowersterile needle chambers 143,144. The upper end of upper needle chamber143 is closed by an axially slidable bung 145, whilst the lower end oflower needle chamber 144 is closed by an axially slidable bung 146.Beads 147 are provided on the inner wall of the needle hub serving bothto locate the bungs 145,146 in the positions shown in FIG. 13 and alsoto vent air from the needle chambers 143,144 when the bungs are pushedonto the needle 10.

FIG. 12 shows the condition of the pack when vial 7 has been pushed intohousing 17 such that it pushes bung 145 downwardly to cause penetrationby needle 10 of both the bung 145 and the bung 24 which forms the vialclosure. It will be appreciated that during the penetration action thesharp end of needle 10 pierces through the two bungs sequentially and isthus maintained in sterile conditions at all times.

Lower bung 146 is shown in FIG. 12 prior to axial upward movementthereof. This will be effected by pushing of the cartridge 3 upwardly(after cap 18 has been removed) to cause the needle 10 to penetratefirst through bung 146 and then through seal 23 of the cartridge.

It will be appreciated that whilst the pack 70 shown in FIG. 12 issuitable for use with a constitution device such as that shown in FIG.7, it may also be used to reconstitute a drug formulation without such adevice. Thus a plunger rod 150 (see FIG. 15) may be screwed into thread130 of plunger 21 and then used manually to push plunger 21 into thecartridge 3. A patient may be supplied with the pack 70 with or withouta cartridge 3 and vial 7 already in place. It will generally bepreferred for the vial and the cartridge to be preassembled in the pack.The plunger rod 150 may be supplied ready assembled or separately sothat the user has to screw it to the plunger 21. The drug vial 7 isfirst pushed inwardly onto the needle, followed by the cartridge.Plunger rod 150 is used manually to transfer the contents of thecartridge to the vial, the pack is inverted and the reconstituted drugis pulled back into the cartridge. The cartridge is removed from thepack and the pack is thrown away.

A moulded housing 151 for the cartridge is shown in FIG. 15. Thecartridge 3 is clipped into the housing 151, where it is held by a lip152. A standard injection needle 153 is attached to the end of thecartridge 3 and the drug is injected. The syringe and needle are thendiscarded. Alternatively, the cartridge could be inserted into anautoinjector.

FIG. 16 shows an alternative form of needle assembly 140, for use with aprefilled syringe. This is similar to the design of FIG. 12, except thatinstead of providing a double-ended needle 10 a Luer fitting 160 isprovided. The sharp end of the needle 10 is kept sterile by a bung 146,as in the case of FIG. 12, whilst the Luer end is kept sterile with aseal 161 of a suitable film, such as Tyvek (registered trade mark). Toreconstitute the drug a user pushes the vial 7 into the housing 17 so asto push the bung 146 axially. The bung 146 and the seal 23 of the vial 7are pierced by the needle 10. The seal 161 is then either peeled off andthe pre-filled syringe fastened to the Luer fitting or the seal ispierced with the syringe's nozzle prior to attaching the syringe to theLuer fitting. Reconstitution of the drug takes place as describedpreviously and the syringe containing the reconstituted drug is removed.An injection needle is fastened to the syringe and the doseadministered. The pack is discarded.

It will be appreciated that the needle hub 140 could be elongated, thusobviating the need for the housing 17. This could make the overall unitless expensive. It will also be appreciated that, as with the FIG. 12arrangement, the end of the needle 10 which enters the vial 7 is keptsterile at all times and that the vial is preferably removable wherebymore than one vial can be used with one syringe of diluent.

What is claimed is:
 1. A device for reconstituting liquid for medicaluse by bringing together a first liquid medium contained in a firstvessel, the device comprising a support for the first and secondvessels, a moveable operating member, and a driver for automaticallymoving the moveable operating member for applying a force to cause thefirst liquid medium to be delivered at a controlled rate from the firstvessel into the second vessel, wherein the moveable operating member isreversibly operable to cause the combined first and second media to bedelivered from the second vessel into the first vessel.
 2. A device asclaimed in claim 1, comprising a weight to provide the force to effectdelivery.
 3. A device as claimed in claim 1, comprising one or moresprings to provide the force to effect delivery.
 4. A device as claimedin claim 1, wherein movement of the movable operating member iscontrolled at least partly by the flow of gas via a restricted flowpath.
 5. A device as claimed in claim 1, comprising a housing whichhouses the support for the first and second vessels and the movableoperating member.
 6. A device as claimed in claim 1, wherein anarrangement of relatively movable coaxial tubular members is provided toguide the movement of the movable operating member.
 7. A device asclaimed in claim 1, wherein the movable operating member is arranged toengage a movable portion of the first vessel to urge the movable portionin an axial direction.
 8. A device as claimed in claim 1, comprising anindicator for indicating the status of delivery.
 9. A device as claimedin claim 8, wherein the indicator provides a visual indication of theposition of the movable operating member.
 10. A device as claimed inclaim 1, combination with a pack removably insertable in the device. 11.A device and a pack as claimed in claim 10, wherein the pack includesthe first vessel containing the first liquid medium, the second vesselcontaining the second medium, or both.
 12. A device and a pack asclaimed in claim 10, wherein the pack includes a liquid transfer devicefor transferring liquid from the first vessel into the second vessel,the liquid transfer device being shielded by a housing of the pack. 13.A device and a pack as claimed in claim 11, wherein the pack has aremovable tamper evident cap.
 14. A device and a pack as claimed inclaim 10, wherein the device has an engagement member for engaging thepack to cause the first and second vessels to be placed in liquidcommunication.
 15. Use of a device as claimed in claim 1, forreconstituting a pharmaceutical liquid.
 16. Use as claimed in claim 15,for reconstituting a pharmaceutical liquid formulation comprising a drugand a diluent or carrier.
 17. A kit for reconstituting a liquid formedical use by bringing together a first liquid medium contained in afirst vessel and a second medium contained in a second vessel, the kitcomprising a pack for holding the first and second vessels, and a devicein which the pack is removably insertable, the kit being operable tobring the first liquid medium and the second medium together bytransferring the first liquid medium from the first vessel to the secondvessel and being operable to transfer the combined first and secondmedia from the second vessel to the first vessel, wherein the pack isarranged to hold the first vessel removably so that, in use, aftertransfer of the first liquid medium from the first vessel to the secondvessel and transfer of the combined first and second media from thesecond vessel to the first vessel, the first vessel may be removed fromthe pack together with the combined first and second media containedtherein.
 18. A kit as claimed in claim 17, wherein the device has anengagement device for engaging the pack to cause the first and secondvessels to be placed in liquid communication.
 19. A kit as claimed inclaim 17, comprising a liquid communication device arranged to accessthe second vessel before it accesses the first vessel.
 20. A pack forreconstituting a liquid for medical use by bringing together a firstliquid medium contained in a first vessel and a second medium containedin a second vessel, the pack comprising a holder for the first andsecond vessels, a liquid transfer device for placing the vessels inliquid communication, said liquid transfer device including a firstpenetrating member for penetrating a closure of the second vessel, asecond penetrating member for penetrating a closure of the first vessel,and a shield for shielding a user from the penetrating members before,during and after liquid reconstitution, wherein the pack furthercomprises protective members for the first and second penetratingmembers arranged such that when the first penetrating member and secondvessel closure are brought together the first penetrating memberpenetrates both a protective member and the second vessel closure, andwhen the second penetrating member and the first vessel closure arebrought together the second penetrating member penetrates both aprotective member and the first vessel closure.
 21. A pack forreconstituting a liquid for medical use by bringing together a firstliquid medium contained in a first vessel and a second medium containedin a second vessel, the pack comprising a holder for the first andsecond vessels, a liquid transfer device for placing the vessels inliquid communication, said liquid transfer device including a firstpenetrating member for penetrating a closure of the second vessel, asecond penetrating member for penetrating a closure of the first vessel,wherein the first and second penetrating members are arranged to bemaintained in a sterile environment at all times prior to penetration ofthe first and second vessel closures, and wherein the pack furthercomprises protective members for the first and second penetratingmembers arranged such that when the first penetrating member and secondvessel closure are brought together the first penetrating memberpenetrates both a protective member and the second vessel closure, andwhen the second penetrating member and the first vessel closure arebrought together the second penetrating member penetrates both aprotective member and the first vessel closure.
 22. A pack as claimed inclaim 20, wherein the protective members are sheaths on the first andsecond penetrating members.
 23. A pack as claimed in claim 20, whereinthe protective members are bungs.
 24. A pack as claimed in claim 23,wherein the bungs are arranged to be pushed on e first and secondpenetrating members by the first and second vessels.
 25. A pack asclaimed in claim 24, comprising a vent for venting gas from the sterileenvironment around the first and second penetrating members when thebungs are pushed.
 26. A pack as claimed in claim 20, wherein the liquidtransfer device is arranged in a tubular housing for receiving the firstvessel at one end and the second vessel at the opposite end.
 27. A packas claimed in claim 1, arranged to hold the second vessel removably. 28.A pack as claimed in claim 21, wherein the protective members aresheaths on the first and second penetrating members.
 29. A pack asclaimed in claim 21, wherein the protective members are bungs.
 30. Apack as claimed in claim 29, wherein the bungs are arranged to be pushedonto the first and second penetrating members by the first and secondvessels.
 31. A pack as claimed in claim 30, comprising a vent forventing gas from the sterile environment around the first and secondpenetrating members when the bungs are pushed.
 32. A pack as claimed inclaim 21, wherein the liquid transfer device is arranged in a tubularhousing for receiving the first vessel at one end and the second vesselat the opposite end.